Weinberger Myron H, White William B, Ruilope Luis-Miguel, MacDonald Thomas M, Davidson Robert C, Roniker Barbara, Patrick Jeffrey L, Krause Scott L
Hypertension Research Center, Indiana University School of Medicine, Indianapolis, IN 46202-5111, USA.
Am Heart J. 2005 Sep;150(3):426-33. doi: 10.1016/j.ahj.2004.12.005.
Sodium retention and volume expansion, mediated in part by aldosterone, are prominent features in low-renin hypertension. Agents that block aldosterone at its receptor sites, therefore, should have significant clinical benefit in patients with low-renin hypertension.
This 16-week, multicenter, double-blind, active-controlled, parallel-group, titration-to-effect trial compared the blood pressure and neurohumoral responses of the selective aldosterone blocker eplerenone (100-200 mg/d; n = 86) with those of the angiotensin receptor blocker losartan (50-100 mg/d; n = 82) in patients with low-renin hypertension (active renin < or = 25 pg/mL [< or = 42.5 mU/L]). Patients with diastolic blood pressure > or = 90 mm Hg after 8 weeks of monotherapy received add-on therapy with hydrochlorothiazide 12.5 to 25 mg daily.
After 8 weeks of therapy, eplerenone reduced blood pressure to a greater extent than losartan (systolic blood pressure -15.8 vs -10.1 mm Hg, P = .017; diastolic blood pressure -9.3 vs -6.7 mm Hg, P = .05). After 16 weeks of therapy, significantly fewer eplerenone-treated patients (32.5%) than losartan-treated patients (55.6%) required add-on hydrochlorothiazide as allowed per protocol for blood pressure control (P = .003). Eplerenone consistently reduced blood pressure regardless of baseline active plasma renin levels whereas losartan reduced blood pressure more effectively in patients with higher baseline active renin levels. There were no differences between treatments in adverse events (reported by 62.8% of eplerenone patients and by 72.0% of losartan patients).
These data show that eplerenone was more effective than losartan in reducing blood pressure in patients with low-renin hypertension. Further studies evaluating the efficacy of eplerenone in difficult-to-treat or resistant hypertension are needed.
钠潴留和容量扩张在低肾素性高血压中是突出特征,部分由醛固酮介导。因此,在醛固酮受体位点阻断醛固酮的药物对低肾素性高血压患者应具有显著的临床益处。
这项为期16周的多中心、双盲、活性药物对照、平行组、根据效应调整剂量的试验,比较了选择性醛固酮阻断剂依普利酮(100 - 200mg/天;n = 86)与血管紧张素受体阻断剂氯沙坦(50 - 100mg/天;n = 82)对低肾素性高血压(活性肾素≤25pg/mL[≤42.5mU/L])患者的血压和神经体液反应。单药治疗8周后舒张压≥90mmHg的患者接受每日12.5至25mg氢氯噻嗪的附加治疗。
治疗8周后,依普利酮降低血压的程度大于氯沙坦(收缩压 - 15.8对 - 10.1mmHg,P = 0.017;舒张压 - 9.3对 - 6.7mmHg,P = 0.05)。治疗16周后,按照方案允许用于血压控制的情况,依普利酮治疗的患者(32.5%)需要附加氢氯噻嗪的人数显著少于氯沙坦治疗的患者(55.6%)(P = 0.003)。无论基线活性血浆肾素水平如何,依普利酮持续降低血压,而氯沙坦在基线活性肾素水平较高的患者中更有效地降低血压。治疗组之间不良事件无差异(依普利酮患者报告率为62.8%,氯沙坦患者报告率为72.0%)。
这些数据表明,依普利酮在降低低肾素性高血压患者血压方面比氯沙坦更有效。需要进一步研究评估依普利酮在难治性或顽固性高血压中的疗效。